7UX0

Human Sperm TMEM95 Ectodomain

Summary for 7UX0

• Entry DOI: 10.2210/pdb7ux0/pdb
• Descriptor: Sperm-egg fusion protein TMEM95, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, TRIETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: fertilization, sperm-egg binding, sperm-egg fusion, acrosomal membrane protein, cell adhesion
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 14687.88

Authors

Tang, S.,Kim, P.S. (deposition date: 2022-05-04, release date: 2022-10-12, Last modification date: 2024-11-06)

Primary citation

Tang, S.,Lu, Y.,Skinner, W.M.,Sanyal, M.,Lishko, P.V.,Ikawa, M.,Kim, P.S.
Human sperm TMEM95 binds eggs and facilitates membrane fusion.
Proc.Natl.Acad.Sci.USA, 119:e2207805119-e2207805119, 2022

PubMed Abstract: encodes a sperm acrosomal membrane protein, whose knockout has a male-specific sterility phenotype in mice. knockout murine sperm can bind to, but do not fuse with, eggs. How TMEM95 plays a role in membrane fusion of sperm and eggs has remained elusive. Here, we utilize a sperm penetration assay as a model system to investigate the function of human TMEM95. We show that human TMEM95 binds to hamster egg membranes, providing evidence for a TMEM95 receptor on eggs. Using X-ray crystallography, we reveal an evolutionarily conserved, positively charged region of TMEM95 as a putative receptor-binding surface. Amino acid substitutions within this region of TMEM95 ablate egg-binding activity. We identify monoclonal antibodies against TMEM95 that reduce the number of human sperm fused with hamster eggs in sperm penetration assays. Strikingly, these antibodies do not block binding of sperm to eggs. Taken together, these results provide strong evidence for a specific, receptor-mediated interaction of sperm TMEM95 with eggs and suggest that this interaction may have a role in facilitating membrane fusion during fertilization.

PubMed: 36161911
DOI: 10.1073/pnas.2207805119

Experimental method

X-RAY DIFFRACTION (1.49 Å)